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Objectives In 2012, onetime hepatitis C virus (HCV) screening was recommended for all baby boomers (people born during 1945-1965) in the United States, but only 4.0%-12.9% of baby boomers have ever had a screening ordered by a health care provider. This study examined the HCV screening prevalence among adult patients in a large academic health care system and assessed factors associated with the completion of screening when ordered for baby boomers. Methods We defined HCV screening completion as the completion of an HCV antibody test when it was ordered. We used electronic health records to examine HCV screening completion rates among adults (N = 106 630) from August 1, 2015, through July 31, 2020, by birth cohort. Among baby boomers whose health care provider ordered HCV screening, we examined frequency and percentages of HCV screening completion by sociodemographic and clinical characteristics. We conducted univariate and multivariable logistic regression analyses to assess factors associated with HCV screening completion among baby boomers. Results During the study period, 73.0% of baby boomers completed HCV screening when it was ordered. HCV completion did not differ by sex or race and ethnicity among baby boomers. Baby boomers with Medicare supplemental health insurance compared with commercial health insurance (adjusted odds ratio [aOR] = 1.87) and those seeing only advanced practice professionals compared with specialty care physicians (aOR = 2.24) were more likely to complete HCV screening when it was ordered. Conclusions Noncompletion of HCV screening is one of many barriers along the HCV treatment continuum. Our findings suggest a need for interventions targeting systems, health care providers, and patients to increase HCV screening rates in the United States.

BACKGROUND: There is a gap between the necessity of effective mental health interventions in the workplace and the availability of evidence-based information on how to evaluate them. The available evidence outlines that mental health interventions should follow integrated approaches combining multiple components related to different levels of change. However, there is a lack of robust studies on how to evaluate multicomponent workplace interventions which target a variety of outcomes at different levels taking into account the influence of different implementation contexts. METHOD: We use the MENTUPP project as a research context to develop a theory-driven approach to facilitate the evaluation of complex mental health interventions in occupational settings and to provide a comprehensive rationale of how these types of interventions are expected to achieve change. We used a participatory approach to develop a ToC involving a large number of the project team representing multiple academic backgrounds exploiting in tandem the knowledge from six systematic reviews and results from a survey among practitioners and academic experts in the field of mental health in SMEs. RESULTS: The ToC revealed four long-term outcomes that we assume MENTUPP can achieve in the workplace: 1) improved mental wellbeing and reduced burnout, 2) reduced mental illness, 3) reduced mental illness-related stigma, and 4) reduced productivity losses. They are assumed to be reached through six proximate and four intermediate outcomes according to a specific chronological order. The intervention consists of 23 components that were chosen based on specific rationales to achieve change on four levels (employee, team, leader, and organization). CONCLUSIONS: The ToC map provides a theory of how MENTUPP is expected to achieve its anticipated long-term outcomes through intermediate and proximate outcomes assessing alongside contextual factors which will facilitate the testing of hypotheses. Moreover, it allows for a structured approach to informing the future selection of outcomes and related evaluation measures in either subsequent iterations of complex interventions or other similarly structured programs. Hence, the resulting ToC can be employed by future research as an example for the development of a theoretical framework to evaluate complex mental health interventions in the workplace. ispartof: BMC PUBLIC HEALTH vol:23 issue:1 ispartof: location:England status: published

Objectives Chronic hepatitis C virus (HCV) infection is one of the main causes of hepatocellular carcinoma. Before initiating a multilevel HCV screening intervention, we sought to (1) describe concordance between the electronic health record (EHR) data warehouse and manual medical record review in recording aspects of HCV testing and treatment and (2) estimate the percentage of patients with chronic HCV infection who initiated and completed HCV treatment using manual medical record review. Methods We examined the medical records for 177 patients (100 randomly selected patients born during 1945-1965 without evidence of HCV testing and 77 adult patients of any birth cohort who had completed HCV testing) with a primary care or relevant specialist visit at an academic health care system in Tampa, Florida, from 2015 through 2018. We used the Cohen κ coefficient to examine the degree of concordance between the searchable data warehouse and the medical record review abstractions. Descriptive statistics characterized referral to and receipt of treatment among patients with chronic HCV infection from medical record review. Results We found generally good concordance between the data warehouse abstraction and medical record review for HCV testing data (κ ranged from 0.66 to 0.87). However, the data warehouse failed to capture data on HCV treatment variables. According to medical record review, 28 patients had chronic HCV infection; 16 patients were prescribed treatment, 14 initiated treatment, and 9 achieved and had a reported posttreatment undetected HCV viral load. Conclusions Using data warehouse data provides generally reliable HCV testing information. However, without the use of natural language processing and purposeful EHR design, manual medical record reviews will likely be required to characterize treatment initiation and completion.

Using loan-level data covering two-thirds of all corporate loans from U.S. banks, we document that SMEs (i) obtain much shorter maturity credit lines than large firms; (ii) have less active maturity management and therefore frequently have expiring credit; (iii) post more collateral on both credit lines and term loans; (iv) have higher utilization rates in normal times; and (v) pay higher spreads, even conditional on other firm characteristics. We present a theory of loan terms that rationalizes these facts as the equilibrium outcome of a trade-off between commitment and discretion. We test the model's prediction that small firms may be unable to access liquidity when large shocks arrive using data on drawdowns in the COVID recession. Consistent with the theory, the increase in bank credit in 2020Q1 and 2020Q2 came almost entirely from drawdowns by large firms on pre-committed lines of credit. Differences in demand for liquidity cannot fully explain the differences in drawdown rates by firm size, as we show that large firms also exhibited much higher sensitivity of drawdowns to industry-level measures of exposure to the COVID recession. Finally, we match the bank data to a list of participants in the Paycheck Protection Program (PPP) and show that SME recipients of PPP loans reduced their non-PPP bank borrowing in 2020Q2 by between 53 and 125 percent of the amount of their PPP funds, suggesting that government-sponsored liquidity can overcome private credit constraints.

The 2015 Magnetic Resonance Imaging in Multiple Sclerosis and 2016 Consortium of Multiple Sclerosis Centres guidelines on the use of MRI in diagnosis and monitoring of multiple sclerosis made an important step towards appropriate use of MRI in routine clinical practice. Since their promulgation, there have been substantial relevant advances in knowledge, including the 2017 revisions of the McDonald diagnostic criteria, renewed safety concerns regarding intravenous gadolinium-based contrast agents, and the value of spinal cord MRI for diagnostic, prognostic, and monitoring purposes. These developments suggest a changing role of MRI for the management of patients with multiple sclerosis. This 2021 revision of the previous guidelines on MRI use for patients with multiple sclerosis merges recommendations from the Magnetic Resonance Imaging in Multiple Sclerosis study group, Consortium of Multiple Sclerosis Centres, and North American Imaging in Multiple Sclerosis Cooperative, and translates research findings into clinical practice to improve the use of MRI for diagnosis, prognosis, and monitoring of individuals with multiple sclerosis. We recommend changes in MRI acquisition protocols, such as emphasising the value of three dimensional-fluid-attenuated inversion recovery as the core brain pulse sequence to improve diagnostic accuracy and ability to identify new lesions to monitor treatment effectiveness, and we provide recommendations for the judicious use of gadolinium-based contrast agents for specific clinical purposes. Additionally, we extend the recommendations to the use of MRI in patients with multiple sclerosis in childhood, during pregnancy, and in the post-partum period. Finally, we discuss promising MRI approaches that might deserve introduction into clinical practice in the near future.

Hospitalized patients with severe obesity require adapted hospital management. The aim of this study was to evaluate a machine learning model to predict in-hospital mortality among this population.Data of unselected consecutive emergency department admissions of hospitalized patients with severe obesity (BMI ≥ 40 kg/mA total of 14,078 hospital admissions of inpatients with severe obesity were included. The in-hospital mortality rate was 297/14,078 (2.1%). In univariate analysis, albumin (area under the curve [AUC] = 0.77), blood urea nitrogen (AUC = 0.76), acuity level (AUC = 0.73), lactate (AUC = 0.72), and chief complaint (AUC = 0.72) were the best single predictors. For Youden's index, the model had a sensitivity of 0.77 (95% CI: 0.67-0.86) with a false positive rate of 1:9.A machine learning model trained on clinical measures provides proof of concept performance in predicting mortality in patients with severe obesity. This implies that such models may help to adopt specific decision support tools for this population.

Objectives Bipolar disorder (BD) has a highly heterogeneous clinical course that is characterized by relapses and increased health care utilization in a significant fraction of patients. A thorough understanding of factors influencing illness course is essential for predicting disorder severity and developing targeted therapies. Methods We performed polygenic score analyses in four cohorts (N = 954) to test whether the genetic risk for BD, schizophrenia, or major depression is associated with a severe course of BD. We analyzed BD patients with a minimum illness duration of five years. The severity of the disease course was assessed by using the number of hospitalizations in a mental health facility and a composite measure of longitudinal illness severity (OPCRIT item 90). Results Our analyses showed that higher polygenic scores for BD (β = 0.11, SE = 0.03, p = 1.17 × 10-3) and schizophrenia (β = 0.09, SE = 0.03, p = 4.24 × 10-3), but not for major depression, were associated with more hospitalizations. None of the investigated polygenic scores was associated with the composite measure of longitudinal illness severity (OPCRIT item 90). Limitations We could not account for non-genetic influences on disease course. Our clinical sample contained more severe cases. Conclusions This study demonstrates that the genetic risk burden for psychiatric illness is associated with increased health care utilization, a proxy for disease severity, in BD patients. The findings are in line with previous observations made for patients diagnosed with schizophrenia or major depression. Therefore, in the future psychiatric disorder polygenic scores might become helpful for stratifying patients with high risk of a chronic manifestation and predicting disease course.

The subthalamic nucleus and internal pallidum are main target sites for deep brain stimulation in Parkinson’s disease. Multiple trials that investigated subthalamic versus pallidal stimulation were unable to settle on a definitive optimal target between the two. One reason could be that the effect is mediated via a common functional network. To test this hypothesis, we calculated connectivity profiles seeding from deep brain stimulation electrodes in 94 patients that underwent subthalamic and 28 patients with pallidal treatment based on a normative connectome atlas calculated from 1000 healthy subjects. In each cohort, we calculated connectivity profiles that were associated with optimal clinical improvements. The two maps showed striking similarity and were able to cross-predict outcomes in the respective other cohort (R = 0.37 at P < 0.001; R = 0.34 at P = 0.032). Next, we calculated an agreement map, which retained regions common to both target sites. Crucially, this map was able to explain an additional amount of variance in clinical improvements of either cohort when compared to the maps calculated on each cohort alone. Finally, we tested profiles and predictive utility of connectivity maps calculated from different motor symptom subscores with a specific focus on bradykinesia and rigidity. While our study is based on retrospective data and indirect connectivity metrics, it may deliver empirical data to support the hypothesis of a largely overlapping network associated with effective deep brain stimulation in Parkinson’s disease irrespective of the specific target.

Background: Efficacy of the nine-valent human papillomavirus (9vHPV; HPV types 6/11/16/18/31/33/45/52/58) vaccine was demonstrated in a phase 3 study in women 16 & ndash;26 years of age. We present a phase 3 immunogenicity and safety study of the 9vHPV vaccine in women 27 & ndash;45 versus 16 & ndash;26 years of age. Methods: This international, open-label study (NCT03158220) was conducted in women 16 & ndash;45 years of age. Participants (16 & ndash;26 years, n = 570 and 27 & ndash;45 years, n = 642) received a three-dose 9vHPV vaccination regimen (day 1, month 2, month 6). Month 7 geometric mean titers (GMTs) and seroconversion percentages to anti-HPV 6/11/16/18/31/33/45/52/58 were assessed. Participants were followed for safety throughout the study. Results: At month 7, anti-HPV 6/11/16/18/31/33/45/52/58 GMTs in women 27 & ndash;45 years were compared to those in women 16 & ndash;26 years of age. The primary hypothesis of non-inferiority of anti-HPV 16/18/31/33/45/52/58 GMTs in older versus younger women was met. The lower bound of the GMT ratio 95% confidence interval (27 & ndash;45 years to 16 & ndash;26 years) was 0.60 & ndash;0.67 depending on HPV type, exceeding the non-inferiority margin of 0.5 for all HPV types. Month 7 seroconversion percentages in women 27 & ndash; 45 years of age were >99% for all HPV types. Injection-site and vaccine-related systemic adverse events (AEs) were observed in 87.5% and 25.1% of women 16 & ndash;26 years, and 85.2% and 24.1% of women 27 & ndash; 45 years of age, respectively; no vaccine-related serious AEs were reported and no deaths occurred during the study. Conclusions: The 9vHPV vaccine elicited non-inferior anti-HPV GMTs in women 27 & ndash;45 years compared with women 16 & ndash;26 years of age for HPV 16/18/31/33/45/52/58. The vaccine was generally well tolerated with a similar AE profile across the age groups. These data support bridging 9vHPV vaccine efficacy findings in women 16 & ndash;26 years to women 27 & ndash;45 years of age. Clinical trial registration NCT03158220. (c) 2021 Elsevier Ltd. All rights reserved.

Quantitative MRI provides biophysical measures of the microstructural integrity of the CNS, which can be compared across CNS regions, patients, and centres. In patients with multiple sclerosis, quantitative MRI techniques such as relaxometry, myelin imaging, magnetization transfer, diffusion MRI, quantitative susceptibility mapping, and perfusion MRI, complement conventional MRI techniques by providing insight into disease mechanisms. These include: (i) presence and extent of diffuse damage in CNS tissue outside lesions (normal-appearing tissue); (ii) heterogeneity of damage and repair in focal lesions; and (iii) specific damage to CNS tissue components. This review summarizes recent technical advances in quantitative MRI, existing pathological validation of quantitative MRI techniques, and emerging applications of quantitative MRI to patients with multiple sclerosis in both research and clinical settings. The current level of clinical maturity of each quantitative MRI technique, especially regarding its integration into clinical routine, is discussed. We aim to provide a better understanding of how quantitative MRI may help clinical practice by improving stratification of patients with multiple sclerosis, and assessment of disease progression, and evaluation of treatment response., Quantitative MRI techniques provide biophysical measures of the microstructural integrity of the CNS. Granziera et al. review the information provided by qMRI in the field of multiple sclerosis research and the potential for translation of qMRI techniques into clinical practice.

Evidence for the effectiveness and safety of the third-generation beta-blockers other than atenolol in hypertension remains scarce. We assessed the effectiveness and safety of beta-blockers as first-line treatment for hypertension using three databases in the United States: two administrative claim databases and one electronic health record-based database from 2001 to 2018. In each database, comparative effectiveness of beta-blockers for the risks of acute myocardial infarction, stroke, and hospitalization for heart failure was assessed, using large-scale propensity adjustment and empirical calibration. Estimates were combined across databases using random-effects meta-analyses. Overall, 118,133 and 267,891 patients initiated third-generation beta-blockers (carvedilol and nebivolol) or atenolol, respectively. The pooled hazard ratios of acute myocardial infarction, stroke, hospitalization for heart failure, and most metabolic complications were not different between the third-generation beta-blockers versus atenolol after propensity score matching and empirical calibration (hazard ratio 1.07, 95% CI 0.74 to 1.55 for acute myocardial infarction; hazard ratio 1.06, 95% CI 0.87 to 1.31 for stroke; hazard ratio 1.46, 95% CI 0.99 to 2.24 for hospitalized heart failure). Third-generation beta-blockers were associated with significantly higher risk of stroke than angiotensin-converting enzyme inhibitors (hazard ratio 1.29, 95% CI 1.03 to 1.72), and thiazide diuretics (hazard ratio 1.56, 95% CI 1.17 to 2.20). In conclusion, this study found many patients with first-line beta-blocker monotherapy for hypertension and no statistically significant differences in the effectiveness and safety comparing atenolol with third-generation beta-blockers. Patients on third-generation beta-blockers had a higher risk of stroke than those on angiotensin-converting enzyme inhibitors and thiazide diuretics.

PURPOSE This study compared real-world end points extracted from the Cancer Analysis System (CAS), a national cancer registry with linkage to national mortality and other health care databases in England, with those from diverse US oncology data sources, including electronic health care records, insurance claims, unstructured medical charts, or a combination, that participated in the Friends of Cancer Research Real-World Evidence Pilot Project 1.0. Consistency between data sets and between real-world overall survival (rwOS) was assessed in patients with immunotherapy-treated advanced non–small-cell lung cancer (aNSCLC). PATIENTS AND METHODS Patients with aNSCLC, diagnosed between January 2013 and December 2017, who initiated treatment with approved programmed death ligand-1 (PD-[L]1) inhibitors until March 2018 were included. Real-world end points, including rwOS and real-world time to treatment discontinuation (rwTTD), were assessed using Kaplan-Meier analysis. A synthetic data set, Simulacrum, on the basis of conditional random sampling of the CAS data was used to develop and refine analysis scripts while protecting patient privacy. RESULTS Characteristics (age, sex, and histology) of the 2,035 patients with immunotherapy-treated aNSCLC included in the CAS study were broadly comparable with US data sets. In CAS, a higher proportion (46.7%) of patients received a PD-(L)1 inhibitor in the first line than in US data sets (18%-30%). Median rwOS (11.4 months; 95% CI, 10.4 to 12.7) and rwTTD (4.9 months; 95% CI, 4.7 to 5.1) were within the range of US-based data sets (rwOS, 8.6-13.5 months; rwTTD, 3.2-7.0 months). CONCLUSION The CAS findings were consistent with those from US-based oncology data sets. Such consistency is important for regulatory decision making. Differences observed between data sets may be explained by variation in health care settings, such as the timing of PD-(L)1 approval and reimbursement, and data capture.

BACKGROUND Treatment of prurigo nodularis (PN) is challenging and new treatment options are needed. OBJECTIVE To evaluate the efficacy and safety of two oral doses of the kappa opioid agonist and mu opioid antagonist nalbuphine extended release (NAL-ER) tablets in a phase 2, multicentre, randomized, double-blind, placebo-controlled trial with an open-label, 50-week extension phase. METHODS Subjects with moderate-to-severe PN were randomized to NAL-ER 81 mg (NAL-ER81) or 162 mg (NAL-ER162) tablets twice-daily or placebo for 8 weeks of stable dosing following a 2-week titration period. Subjects completing Week 10 with a Worst Itch Numerical Rating Scale (WI-NRS) score ≥5 at the time of rollover (or during the observation period) were eligible for open-label treatment. RESULTS Of 63 randomized subjects, 62 were treated and comprised the modified intent-to-treat population (MITT), 50 completed 10 weeks of treatment. In the MITT analysis, 8 subjects (44.4%) treated with NAL-ER162 (P = 0.32) and 6 (27.3%) treated with NAL-ER81 (P = 0.78) achieved ≥30% reduction from baseline in 7-day WI-NRS at Week 10 (primary efficacy endpoint) vs. 8 (36.4%) in the placebo group. Itch reduction was significant among 8/12 (66.7%) subjects completing Week 10 treated with NAL-ER162 vs. placebo (8/20, 40.0%; P = 0.03). Additionally, 6 subjects (33.3%) treated with NAL-ER162 and 3 (13.6%) treated with NAL-ER81 achieved ≥50% reduction from baseline in 7-day WI-NRS at Week 10 (coprimary endpoint). Extended open-label treatment was associated with further improvements in itch reduction and favourable changes in PN lesion activity as assessed by Prurigo Activity Score. Adverse events occurred predominantly during dose titration and were of mild-to-moderate severity. The safety profile did not change with extended open-label treatment. CONCLUSION In adult subjects with PN, oral treatment with NAL-ER 162 mg twice daily provided measurable anti-pruritic efficacy in subjects completing ≥10 weeks of treatment and was well tolerated (ClinicalTrials.gov: NCT02174419).

BACKGROUND Risankizumab has demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis in randomized clinical trials. OBJECTIVES To evaluate safety data from risankizumab psoriasis phase I-III clinical trials. METHODS Short-term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long-term safety was evaluated using integrated data from 17 phase I-III completed and ongoing trials. RESULTS Short-term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient-years (PY) of exposure, respectively]. Long-term analyses included 3072 risankizumab-treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure-adjusted adverse event rates did not increase with long-term treatment (318 vs. 171 events per 100 PY for short- and long-term analyses). With long-term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients. CONCLUSIONS Risankizumab demonstrated a favourable safety profile over short- and long-term treatment in patients with moderate-to-severe psoriasis.

Background Healthcare personnel (HCP) knowledge and attitudes toward infection control measures are important determinants of practices that can protect them from transmission of infectious diseases. Methods Healthcare personnel were recruited from Emergency Departments and outpatient clinics at seven sites. They completed knowledge surveys at the beginning and attitude surveys at the beginning and end of each season of participation. Attitudes toward infection prevention and control measures, especially medical masks and N95 respirators, were compared. The proportion of participants who correctly identified all components of an infection control bundle for seven clinical scenarios was calculated. Results The proportion of participants in the medical mask group who reported at least one reason to avoid using medical masks fell from 88.5% on the pre-season survey to 39.6% on the post-season survey (odds ratio [OR] for preseason vs. postseason 0.11, 95% CI 0.10-0.14). Among those wearing N95 respirators, the proportion fell from 87.9% to 53.6% (OR 0.24, 95% CI 0.21-0.28). Participants correctly identified all components of the infection control bundle for 4.9% to 38.5% of scenarios. Conclusions Attitudes toward medical masks and N95 respirators improved significantly between the beginning and end of each season. The proportion of HCP who correctly identified the infection control precautions needed for clinical scenarios was low, but it improved over successive years of participation in the study.

The U.S. government procures more than $500 billion annually in goods and services on public contracts, which it classifies using a hierarchical product and service taxonomy. Classification serves several purposes, including transparency in the use of taxpayer funding; reporting, tracing, and segmenting government expenditures; budgeting; and forecasting. Government acquisition personnel have historically performed these classifications manually, resulting in a process that is time-consuming and error-prone and offers limited visibility into government purchases. The problem faced is not unique to the public sector and is common across retail, manufacturing, and healthcare, among other settings. Using almost 4 million historical data records on governmental purchases, we fit a series of classifiers and demonstrate (a) superior performance when explicitly modeling the hierarchical structure of information domains through the use of top-down strategies and (b) the effectiveness of character-level convolutional neural networks when textual inputs are terse and contain irregularities such as abnormal character combinations and misspellings, which are common in government contracts. Our machine learning models are embedded in multiple software applications, including a web application that we developed, used by federal government personnel and other contracting professionals.

Child and adolescent mental health systems are facing limited resources of available psychosocial interventions, often leading to long waiting lists for acceptance to treatment. We describe the feasibility of a short-term (8–10 sessions) psychological crisis intervention (CI) protocol for children and adolescents aged 8–17 years (n = 30, mean ± standard deviation 12.9 ± 2.4 years) who were referred to an outpatient mental health clinic due to suicidal ideation, aggression, severe anxiety, or extreme family conflict. The participants were assessed before and after the CI, and at a 3–6-months follow-up visit. The psychiatric assessments included clinical evaluation by a senior psychiatrist, and the completion of self-report questionnaires by both the participants and their parents. Following the establishment of the CI unit, the waiting lists for urgent cases were reduced from a median of 84 days in the two preceding years to 23 days in the following 3 years (H[2] = 18.5, p

The recent advent of numerous clinical trials for the treatment of moderate-to-severe atopic dermatitis has led to new and emerging therapeutic options for this chronic inflammatory skin disease. With this rapid development has come a lack of consistency in study designs, trial conduct, and statistical analyses. Healthcare providers are challenged to interpret how variations in study parameters may influence clinical trial results. Based on literature review and our experience as clinical trialists, we compiled a list of 22 key study parameters of contemporary clinical trials in moderate-to-severe atopic dermatitis and ranked the top study parameters that may have a significant effect on efficacy results. The top parameters included study comparators, rules for rescue treatment, washout periods for topical and systemic treatments, inclusion criteria such as disease severity by Eczema Area and Severity Index and/or Investigator Global Assessment scores, and the duration of the screening period. We describe considerations for these key parameters, with a focus on between-parameter interactions and effect on efficacy results. This may serve to inform the interpretation of atopic dermatitis clinical trials and raise the profile of the need to harmonize the clinical trial design., Plain Language Summary Atopic dermatitis (AD) is a skin disease characterized by red, itchy skin that is highly burdensome for patients. Patients with moderate-to-severe disease have large, inflamed skin areas with frequent itching. Recently, the number of clinical trials for drugs that treat moderate-to-severe AD has rapidly increased, with differences in how these trials are designed. There is a need for healthcare providers examining results from different clinical trials to understand how trial design factors might influence study outcomes. In this article, we identify key trial design factors that impact study outcomes, detail how these factors can impact clinical trial results, and explore how these factors interact with one another to affect study outcomes. The five most important design factors, as determined via author surveys, were study comparators (a placebo and/or another drug to which the drug being studied is compared); the rules for the use of rescue treatment (a form of treatment given if an enrolled participant has uncontrolled AD symptoms); washout periods (the time before the trial when previous treatments are stopped to allow them to be cleared from a patient’s system); inclusion criteria (that determine which participants are included); and the length of the screening period (the time when patients are assessed to determine if they qualify for participation). By understanding how these key trial design factors impact on study outcomes, healthcare providers may be equipped to better interpret different AD clinical trials. This work also emphasizes the value of harmonizing the AD clinical trial design. Graphic abstract

It has long been known that there is a special affinity of psoriasis for the scalp: Here, it occurs most frequently, lesions terminate sharply in frontal skin beyond the hair line and are difficult to treat. Yet, surprisingly, scalp psoriasis only rarely causes alopecia, even though the pilosebaceous unit clearly is affected. Here, we systematically explore the peculiar, insufficiently investigated connection between psoriasis and growing (anagen) terminal scalp hair follicles (HFs), with emphasis on shared regulatory mechanism and therapeutic targets. Interestingly, several drugs and stressors that can trigger/aggravate psoriasis can inhibit hair growth (e.g. beta-blockers, chloroquine, carbamazepine, interferon-alpha, perceived stress). Instead, several anti-psoriatic agents can stimulate hair growth (e.g. cyclosporine, glucocorticoids, dithranol, UV irradiation), while skin/HF trauma (Köbner phenomenon/depilation) favours the development of psoriatic lesions and induces anagen in "quiescent" (telogen) HFs. On this basis, we propose two interconnected working models: (a) the existence of a bidirectional "hair follicle-psoriasis axis," along which keratinocytes of anagen scalp HFs secrete signals that favour the development and maintenance of psoriatic scalp lesions and respond to signals from these lesions, and (b) that anagen induction and psoriatic lesions share molecular "switch-on" mechanisms, which invite pharmacological targeting, once identified. Therefore, we advocate a novel, cross-fertilizing and integrative approach to psoriasis and hair research that systematically characterizes the "HF-psoriasis axis," focused on identification and therapeutic targeting of selected, shared signalling pathways in the future management of both, psoriasis and hair growth disorders.

ZusammenfassungZink spielt beim Diabetes mellitus eine wichtige Rolle, da das Spurenelement die Insulinbildung, -wirkung und -resistenz beeinflusst. Diabetiker*innen sind für die Ausbildung von Zinkmangelzuständen prädisponiert. Eine hohe Phytataufnahme mit Vollkornprodukten und Hülsenfrüchten vermindert die Bioverfügbarkeit von Zink. Die prophylaktische Zinksupplementation zeigt Studien zufolge positive Effekte bei Prodiabetes und Gestationsdiabetes. Für Erwachsene gilt ein oberer sicherer Dosenbereich (UL) von 25 mg Zink/d in Supplementen.

Background: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. Methods: We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. Results: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%–18% and 1%–14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events. Conclusions: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent. Impact: This study provides epidemiologic characteristics that can inform clinical care and etiologic studies.

The immunopathogenic mechanisms underlying immunoglobulin A nephropathy (IgAN) are poorly understood, yet it is one of the most common causes of kidney failure globally. The commonly referenced syndrome of synpharyngitic gross hematuria as a presenting feature of IgAN has led to a logical association between infections and development of IgAN, however no pathogenic organism has been clearly linked to IgAN. Advances in sequencing technology have enabled more detailed characterization of host microbial communities, and highlighted the interrelationship between microbiota and immune responses in health and disease. This review will summarize current thinking on the relationship between microbiota and development of IgAN with a focus on recent studies relating aberrant mucosal IgA-biased immune responses to microbiota and how this may be related to the immunopathogenesis of IgAN.

Although matrix metalloproteinase 9 (MMP9) has been found associated with various psychiatric disorders and with threat memories in humans, its role in post-traumatic stress disorder (PTSD) and related animal models is understudied. Thus, we analyzed MMP9 mRNA expression kinetics during two different stress experiments, i.e., the Trier Social Stress Test and the dexamethasone suppression test (DST), in whole blood of two independent cohorts of PTSD patients vs. non-traumatized healthy controls (HC) and, moreover, in a mouse model of PTSD and in dexamethasone-treated mice. Besides MMP9, we quantified mRNA levels of four of its regulators, i.e., interleukin (IL)-1 receptor 1 and 2 (IL1R1, IL1R2), IL-6 receptor and tumor necrosis factor receptor 1 (TNFR1) in 10 patients exposed to the DST before vs. after successful PTSD psychotherapy vs. 13 HC and, except from Il6r, also in different brain regions of the PTSD mouse model. We are the first to show that blood MMP9 mRNA concentrations were elevated after acute dexamethasone in PTSD patients, improved upon partial remission of PTSD and were, furthermore, also elevated, together with its regulator Tnfr1, in the prefrontal cortex of PTSDlike mice. In contrast, blood TNFR1 and IL1R2 were markedly underexpressed in PTSD patients. In conclusion, we found translational evidence supporting that, I, TNFR1 and MMP9 mRNA expression might be involved in PTSD pathobiology, II, might constitute potential diagnostic blood biomarkers for PTSD and, importantly, III, post-dexamethasone blood MMP9 hyperexpression, which speculatively results from post-dexamethasone underexpression of IL1R2, might serve also as potential treatment monitoring biomarker for PTSD. (c) 2021 Elsevier B.V. and ECNP. All rights reserved.

Objectives To evaluate a large series of open fractures of the forearm following gunshot wounds in order to determine complication rates and factors that may lead to infection, nonunion, or compartment syndrome. Design Multi-center retrospective review. Setting Nine Level 1 Trauma CentersPatients/Participants: 168 patients had 198 radius and ulna fractures due to firearm injuries. All patients were adults, had a fracture due to a firearm injury and at least one year clinical follow-up or follow-up until union. Average follow-up was 831 days. Intervention Most patients (91%) received antibiotics. Formal irrigation and debridement in the operating room was performed in 75% of cases along with either internal fixation (75%), external fixation (6%), or I&D without fixation (19%). Main outcome measures Complications including neurovascular injuries, compartment syndrome, infection and nonunion. Results Twenty-one percent of patients had arterial injuries and 40% had nerve injuries. Nine patients (5%) developed compartment syndrome. Seventeen patients (10%) developed infections, all in comminuted or segmental fractures. Antibiotics were not associated with a decreased risk of infection. Infections in the ulna were more common in fractures with retained bullet fragments and bone loss. Twenty patients (12%) developed a nonunion. Nonunions were associated with high velocity firearms and bone defect size. Conclusions Open fractures of the forearm from gunshot wounds are serious injuries that carry high rates of nonunion and infection. Fractures with significant bone defects are at increased risk of nonunion and should be treated with stable fixation and proper soft tissue handling. Ulna fractures are at particularly high risk for deep infection and septic nonunion and should be treated aggressively. Forearm fractures from gunshot wounds should be followed until union to identify long term complications. Level of evidence Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Kidney international 100(4), 753-779 (2021). doi:10.1016/j.kint.2021.05.015, Published by Elsevier, New York, NY

The aim of this paper is to introduce an innovative workflow for staged reconstruction of the mandible, including the temporomandibular joint (TMJ), using a temporary, patient-specific spacer. In cases of partial mandibular resection including disarticulation, sometimes needed to treat inflammatory bone disease, the spacer is intended to retain symmetry of the hard tissues, to preserve the soft tissues, and to act as a bactericidal agent. When complete healing of the affected surrounding tissues has occurred, final reconstruction using a patient-matched total TMJ endoprosthesis, in combination with an autogenous free bone flap, can be performed as a second-stage procedure. The crucial steps of the workflow are virtual surgical planning, manufacturing of a two-part silicone mold, and chairside manufacturing of the spacer using an established bone cement with gentamycin. The method was first introduced in two patients suffering from therapy-resistant chronic osteomyelitis. The presented protocol of staged surgery allows a much safer and predictable reconstruction compared with immediate reconstruction. The workflow also minimizes the potential risk of endoprosthesis infection - one of the major risks of implant failure.

According to the guidelines of Polish Dermatological Society biological drugs from TNF-alpha inhibitor group (including adalimumab) should not be treated as innovative drugs but as a therapeutic standard, which results from many years of experience of specialists in use of this group of drugs. Treatment with biological drugs from the group of TNF-alpha inhibitors, including adalimumab, can be carried out in outpatient conditions, also in open treatment, outside of therapeutic programs. The eligibility and subsequent monitoring scheme for adalimumab treatment in the outpatient setting should be based on data from the patient’s medical history, provisions of current clinical guidelines, and the summary of product characteristics. According to its registration, adalimumab may be used in adult patients with moderate to severe plaque psoriasis who are candidates for systemic therapy. This provision allows adalimumab to be used both as a first-line generic treatment and after failure (or intolerance) of treatment with another systemic therapy (e.g., methotrexate, cyclosporine, or PUVA).

To achieve a fully connected network in Internet of Things (IoT) there are number of challenges that have to be overcome. Among those, a big challenge is how to keep all of the devices accessible everywhere and every time. In the IoT network, the assumption is that each IoT device can be reached by any client at any given time. In practice, this is not always possible and without a proper mechanism the nodes behind a NAT are unable to communicate with each other directly, and their addresses have to be shared through a trusted third party. This challenge becomes harder by taking into consideration that most NAT traversal approaches have been developed prior to rising of the IoT, without taking into account the constrained nature of the participating devices and mostly depend on a centralized entity. In this paper we proposed the Distributed Address Table (DAT), a decentralized, secure and lightweight address distribution model that allows any two nodes to get the addresses of the other end without relying on a trusted third party. Structured Peer-to-Peer (P2P) overlay by utilizing Distributed Hash Table (DHT) technique is generated as its underlying communication scheme to ensure that all participating devices are accessible at any given time. This is achieved through simple, yet secure and efficient decentralized model. The DAT adopts the edge/fog computing paradigms to ensure a decentralized address distribution. The results showed that the proposed model is efficient. In addition, the security properties of the proposed model have been defined and proved.

Background Probabilistic brain mapping is a promising tool to estimate the expected benefit of pallidal deep brain stimulation (GPi‐DBS) in patients with isolated dystonia (IsoD). Objectives To investigate the role of probabilistic mapping in combined dystonia (ComD). Methods We rendered the pallidal atlas and the volume of tissue activated (VTA) for a cohort of patients with IsoD (n = 20) and ComD (n = 10) that underwent GPi‐DBS. The VTA was correlated with clinical improvement. Afterwards, each VTA was applied on the previously published probabilistic model (Reich et al., 2019). The correlation between predicted and observed clinical benefit was studied in a linear regression model. Results A good correlation between observed and predicted outcome was found for both patients with IsoD (n = 14) and ComD (n = 7) (r2 = 0.32; P

Network meta-analyses (NMAs) increasingly assist in treatment decisions in disease areas such as psoriasis, where data from multiple clinical trials (CTs) on a growing number of different drugs become available. This study aimed to characterize NMAs published in psoriasis. A systematic literature search in PubMed was conducted using a structured search protocol based on the PRISMA criteria. Twenty-seven NMAs were identified, including an average of 43 CTs per NMA. Only eight of 27 NMAs (29.6%) were documented in the PROSPERO registry and only 17 (63%) reported following the PRISMA criteria. The mean number of patients per NMA was 19 624 (range: 6113-51 749). Across all NMAs, the drugs most frequently included were ustekinumab (n = 27 NMAs), followed by adalimumab (n = 25), infliximab and etanercept (n = 24 each). In all n = 27 NMAs, placebo comparisons and in n = 25, comparisons with active controls were used for bridging. Effect estimates were performed in all cases, SUCRA in 14. Most frequently used outcomes were Psoriasis Area and Severity Index (PASI) 75 (n = 25) and PASI 90 (n = 24), and Dermatology Life Quality Index (n = 10). NMAs mostly measured induction efficacy (weeks 10-16, n = 25) but rarely long-term outcomes (weeks 48-56, n = 4). Sensitivity analyses were performed in n = 17 (63%) of the studies. Main results varied considerably between studies and depended on the year of publication and thus the number of available drugs and studies. However, the concordance between NMA efficacy rankings based on PASI 75 was high. Although a large number of NMAs have been published on psoriasis showing highly comparable results on efficacy, no sufficient information on the quality criteria was reported, and PROSPERO registry criteria were not followed. This argues in favour of greater standardization of NMA methodology and reporting.

Introduction Many targeted, systemic therapies have been developed for treatment of moderate-to-severe psoriasis (PsO). A network meta-analysis (NMA) allows for comparison between treatments not directly compared in randomized controlled trials (RCT). This study’s objective was to compare the short-term (10–16 weeks) clinical efficacy according to the Psoriasis Area and Severity Index (PASI) among approved biologic treatments for moderate-to-severe PsO using a novel (enhanced) NMA model. Methods A systematic literature review (SLR) of RCTs for patients with moderate-to-severe PsO was conducted. English publications in MEDLINE, Embase, and The Cochrane Library up to March 2019 were searched. An enhanced multinomial Bayesian NMA was performed to simultaneously adjust for baseline risk and utilize the conditional nature of the PASI (50, 75, 90, and 100) levels. The model relaxes typical constraints that all treatments must have the same ranks across PASI levels. Results The SLR resulted in 319 relevant publications, of which 72 publications from 73 RCTs reporting 10- to 16-week data for at least one PASI response level (30,314 total patients) were included. Interleukin (IL) inhibitors (risankizumab, ixekizumab, brodalumab, secukinumab, and guselkumab) were the best performing treatments for achieving all PASI levels. Etanercept was outperformed by the other subcutaneous tumor necrosis factor α inhibitors. Application of an enhanced NMA model that allowed treatment rankings to differ by PASI level tested the robustness of results of previous NMAs in PsO. Conclusion The results of this model confirmed that IL inhibitors are likely the best short-term treatment choices for improving all PASI levels. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00602-z.

PURPOSE. To capitalize on investments in evidence-based practices, technology is needed to scale up fidelity assessment and supervision. Stakeholder feedback may facilitate adoption of such tools. This evaluation gathered stakeholder feedback and preferences to explore whether it would be fundamentally feasible or possible to implement an automated fidelity-scoring supervision tool in community mental health settings. METHOD. A partially mixed, sequential research method design was used including focus group discussions with community mental health therapists (n=18) and clinical leadership (n=12) to explore typical supervision practices, followed by discussion of an automated fidelity feedback tool embedded in a cloud-based supervision platform. Interpretation of qualitative findings was enhanced through quantitative measures of participants’ use of technology and perceptions of acceptability, appropriateness, and feasibility of the tool. RESULTS. Initial perceptions of acceptability, appropriateness, and feasibility of automated fidelity tools were positive and increased after introduction of an automated tool. Standard supervision was described as collaboratively guided and focused on clinical content, self-care, and documentation. Participants highlighted the tool’s utility for supervision, training, and professional growth, but questioned its ability to evaluate rapport, cultural responsiveness, and non-verbal communication. Concerns were raised about privacy and the impact of low scores on therapist confidence. Desired features included intervention labeling and transparency about how scores related to session content. Opportunities for asynchronous, remote, and targeted supervision were particularly valued. CONCLUSIONS. Stakeholder feedback suggests that automated fidelity measurement could augment supervision practices. Future research should examine the relations among use of such supervision tools, clinician skill, and client outcomes.

OBJECTIVE To noninvasively assess myelin status in chronic white matter lesions of multiple sclerosis (MS), we developed and evaluated a simple classification scheme based on T1 relaxation time maps derived from 7-tesla postmortem and in vivo MRI. METHODS Using the MP2RAGE MRI sequence, we classified 36 lesions from 4 postmortem MS brains as "long-T1," "short-T1," and "mixed-T1" by visual comparison to neocortex. Within these groups, we compared T1 times to histologically derived measures of myelin and axons. We performed similar analysis of 235 chronic lesions with known date of onset in 25 MS cases in vivo and in a validation cohort of 222 lesions from 66 MS cases, investigating associations with clinical and radiological outcomes. RESULTS Postmortem, lesions classified qualitatively as long-T1, short-T1, and mixed-T1 corresponded to fully demyelinated, fully remyelinated, and mixed demyelinated/remyelinated lesions, respectively (p ≤ 0.001). Demyelination (rather than axon loss) dominantly contributed to initial T1 prolongation. We observed lesions with similar characteristics in vivo, allowing manual classification with substantial interrater and excellent intrarater reliability. Short-T1 lesions were most common in the deep white matter, whereas long-T1 and mixed-T1 lesions were prevalent in the juxtacortical and periventricular white matter (p = 0.02) and were much more likely to have paramagnetic rims suggesting chronic inflammation (p

Contains fulltext : 244306.pdf (Publisher’s version ) (Open Access) Patients are the stewards of their own care and hence their voice is important when designing and implementing research. Patients should be involved not only as participants in research that impacts their care, as the recipients of that care and any associated harms, but also as research collaborators in prioritising important questions from the patient perspective and designing the research and the ways in which is it most appropriate to involve patients. The PIONEER Consortium, an international multistakeholder collaboration lead by the European Association of Urology, has developed a core outcome set (COS) for localised and metastatic prostate cancer relevant to all stakeholders in particular patients. Throughout the work of PIONEER, patient representatives were involved as collaborators in setting the research agenda, and a wider group of patients was involved as participants in developing COSs, for instance in consensus meetings on choosing important outcomes and appropriate definitions. This publication showcases the process for COS development and highlights the most important recommendations to ultimately inform future research projects co-created between patients and other stakeholders. PATIENT SUMMARY: An important step in involving patients in the selection of outcomes for clinical trials, clinical audits, and real-world evidence is the development of a core outcome set (COS) that is relevant to all stakeholders. This report highlights the patient participation throughout our PIONEER COS development. TAKE HOME MESSAGE: An important step in involving patients in the selection of outcomes for clinical trials, clinical audits, and real-world evidence is to develop a core outcome set (COS) that is relevant to all stakeholders. As part of the work of the PIONEER Consortium, we aim to highlight the patient participation throughout our PIONEER COS development.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease worldwide. The diagnostic histologic hallmark is dominant or codominant IgA staining on kidney biopsy; however, patients may present with various clinical syndromes ranging from asymptomatic abnormalities noted on urinalysis to rapidly progressive glomerulonephritis. Given substantial heterogeneity in the clinical course of disease, online risk calculators are available that may assist in prognostication and inform discussions with patients. Comprehensive supportive treatment is central in the initial therapy of IgAN; the additive benefit of currently available immunosuppressive agents remains an area of controversy. Although proteinuria is attenuated by the use of corticosteroids, the long-term benefits have been questioned, and the use of corticosteroids is associated with severe adverse effects, notably infection. Recent advances in our understanding of mucosal immunity and the role of the complement system in IgAN pathogenesis are leading to development of novel therapeutic options, which are being evaluated in ongoing clinical trials. In this installment of the AJKD Core Curriculum in Nephrology, IgAN pathogenesis, clinical manifestations, histology, prediction tools, and treatment are reviewed, and case examples are presented to illustrate the approach to the management of patients with IgAN.

Background Frailty is a state of increased vulnerability to stressors, and predicts risk of adverse outcomes, such as mortality. Frailty can be defined by a frailty index (FI) using an accumulation of deficits approach. An FI comprised of 20 items derived from our previously studied test‐based frailty index (TBFI) and an additional 33 survey‐based elements sourced from the standard CGA was developed to evaluate if predictive validity of survival was improved. Methods One hundred eighty‐nine cancer patients during acute hospitalization were consented between September 2018 and May 2019. Frailty scores were calculated, and patients were categorized into four groups: non‐frail (0–0.2), mildly frail (0.2–0.3), moderately frail (0.3–0.4), and severely frail (>0.4). Patients were followed for 1‐year to assess FI and TBFI prediction of survival. Area under the curve (AUC) statistics from ROC analyses were compared for the FI versus TBFI. Results Increasing frailty was similarly associated with increased risk of mortality (HR, 4.5 [95% CI, 2.519–8.075] and HR, 4.1 [95%CI, 1.692–9.942]) and the likelihood of death at 6 months was about 11‐fold (odds ratio, 10.9 [95% CI, 3.97–33.24]) and 9.73‐fold (95% CI, 2.85–38.50) higher for severely frail patients compared to non‐frail patients for FI and TBFI, respectively. This association was independent of age and type of cancer. The FI and TBFI were predictive of survival for older and younger cancer patients with no significant differences between models in discriminating survival (FI AUC, 0.747 [95% CI, 0.6772–0.8157] and TBFI AUC, 0.724 [95% CI, 0.6513–0.7957]). Conclusions The TBFI was predictive of survival, and the addition of an in‐person assessment (FI) did not greatly improve predictive validity. Increasing frailty, as measured by a TBFI, resulted in a meaningfully increased risk of mortality and may be well‐suited for screening of hospitalized cancer patients., A simplified test based frailty index (TBFI) is similarly predictive of survival as a more comprehensive CGA based frailty index in the hospitalized cancer patient. This index may be useful as a screening tool in the acute cancer patient.

Background Moral distress (MD) has been linked to health care professional burnout, intent to leave, and decreased quality of care. Objectives The aim of this study was to describe the perceptions of MD among critical care interdisciplinary team members and assess the association of MD with team member characteristics. Methods A descriptive cross-sectional design was used with interdisciplinary team members in an intensive care unit setting at an NCI-designated Comprehensive Cancer Center in the southeastern United States. The Measure of Moral Distress for Healthcare Professionals was provided to registered nurses, oncology technicians, providers, respiratory therapists, and ancillary team members (social workers, pharmacists, dietitians). Results A total of 67 team members completed the survey. Mean responses for 3 items were higher than 8 (halfway point of scale): "Follow family's insistence to continue aggressive treatment even though I believe it is not in the best interest of patient" (mean [SD], 11.4 [4.8]); "Continue to provide aggressive treatment for a patient most likely to die regardless of this treatment when no one will make a decision to withdraw it" (mean [SD], 10.5 [5.3]); and "Witness providers giving 'false hope' to patient/family" (mean [SD], 9.0 [5.3]). Higher responses on the "Continuing to provide aggressive treatment" item was associated with having "considered leaving due to MD" (P = .027) and "considering leaving now due to MD" (P = .016). Higher total scores were related to having left or considered leaving a job (P = .04). When examining education level, registered nurses with a master's degree (n = 5) exhibited the most MD (P = .04). Conclusion This study suggests that the Measure of Moral Distress for Healthcare Professionals is useful in identifying areas for focused efforts at reducing MD for interdisciplinary teams.

Background Treating to absolute treatment targets rather than relative measures such as Psoriasis Area and Severity Index (PASI)-75 is emerging as an important clinical concept included in psoriasis guidelines and clinical practice. Achieving treatment targets is associated with achievement of long-term outcomes. Objective To evaluate the relationship between psoriasis severity, disease characteristics, and achievement of PASI ≤2 with apremilast in a pooled analysis of the phase 3 ESTEEM 1 and 2 (NCT01194219 and NCT01232283), phase 3b LIBERATE (NCT01690299), and phase 4 UNVEIL (NCT02425826) clinical trials. Methods Pooled data from patients with moderate to severe plaque psoriasis randomized to apremilast 30 mg BID were analyzed by baseline PASI quartiles (Q1: 2.4-13.1, Q2: 13.2-15.9, Q3: 16.0-20.0, Q4: 20.1-57.8). Assessments included PASI, Dermatology Life Quality Index (DLQI), Scalp Physician's Global Assessment (ScPGA, ScPGA ≥1), and target (worst) Nail Psoriasis Severity Index (NAPSI, NAPSI ≥1). Results Of 1,062 patients, 963 had ScPGA ≥1 and 643 had NAPSI ≥1, 771 patients with baseline and Week 32 PASI assessments were included in analyses of Week 32 PASI target achievement. Rates of PASI ≤2 at Week 32 were greater in lower PASI quartiles (Q1: 43.5%, Q2: 31.2%, Q3: 26.8%, Q4: 18.4%). Most patients achieving PASI ≤2 target (83.6%) achieved DLQI ≤5 at Week 32, 59.3% of patients who did not achieve PASI ≤2 target achieved DLQI ≤5. At Week 32, mean improvements in ScPGA and NAPSI were similar with more moderate versus more severe disease (ScPGA, range: 1.1-1.4, NAPSI, range: 1.6-2.5). In a subgroup analysis, achievement of PASI ≤2 target was higher in the lowest PASI quartile and with disease duration Conclusions Greater achievement of PASI ≤2 was observed in patients with more moderate versus more severe skin disease. Apremilast may be particularly beneficial in more moderate disease early in the treatment paradigm.

BACKGROUND Helicoverpa zea (Boddie) damage to Bt cotton and maize has increased as a result of widespread Bt resistance across the USA Cotton Belt. Our objective was to link Bt crop production patterns to cotton damage through a series of spatial and temporal surveys of commercial fields to understand how Bt crop production relates to greater than expected H. zea damage to Bt cotton. To do this, we assembled longitudinal cotton damage data that spanned the Bt adoption period, collected cotton damage data since Bt resistance has been detected, and estimated local population susceptibility using replicated on-farm studies that included all Bt pyramids marketed in cotton. RESULTS Significant year effects of H. zea damage frequency in commercial cotton were observed throughout the Bt adoption period, with a recent damage increase after 2012. Landscape-level Bt crop production intensity over time was positively associated with the risk of H. zea damage in two- and three-toxin pyramided Bt cotton. Helicoverpa zea damage also varied across Bt toxin types in spatially replicated on-farm studies. CONCLUSIONS Landscape-level predictors of H. zea damage in Bt cotton can be used to identify heightened Bt resistance risk areas and serves as a model to understand factors that drive pest resistance evolution to Bt toxins in the southeastern United States. These results provide a framework for more effective insect resistance management strategies to be used in combination with conventional pest management practices that improve Bt trait durability while minimizing the environmental footprint of row crop agriculture. © 2021 Society of Chemical Industry. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Objective:The implementation of mandatory influenza vaccination policies among healthcare personnel (HCP) is controversial. Thus, we examined the affect of mandatory influenza vaccination policies among HCP working in outpatient settings.Setting:Four Veterans’ Affairs (VA) health systems and three non-VA medical centers.Methods:We analyzed rates of influenza and other viral causes of respiratory infections among HCP working in outpatient sites at 4 VA health systems without mandatory influenza vaccination policies and 3 non-VA health systems with mandatory influenza vaccination policies.Results:Influenza vaccination was associated with a decreased risk of influenza (odds ratio, 0.17; 95% confidence interval [CI], 0.13–0.22) but an increased risk of other respiratory viral infections (incidence rate ratio, 1.26; 95% CI, 1.02–1.57).Conclusions:Our fitted regression models suggest that if influenza vaccination rates in clinics where vaccination was not mandated had equalled those where vaccine was mandated, HCP influenza infections would have been reduced by 52.1% (95% CI, 51.3%–53.0%). These observations, their possible causes, and additional strategies to reduce influenza and other viral respiratory illnesses among HCP working in ambulatory clinics warrant further investigation.

Purpose Guselkumab, an interleukin (IL)-23 inhibitor, effectively treats moderate-to-severe plaque psoriasis. Materials and methods ECLIPSE, was a Phase 3, multicenter, 56-week, double-blinded, active-comparator study of guselkumab vs. secukinumab (IL-17A inhibitor) in patients with moderate-to-severe psoriasis. Patients were treated with guselkumab 100 mg (n = 534) or secukinumab 300 mg (n = 514) through week 44. Efficacy (at least a 90% and 100% improvement from baseline in Psoriasis Area and Severity Index [PASI 90 and PASI 100], Investigator's Global Assessment [IGA] 0/1, and IGA 0) was analyzed across subpopulations defined by baseline: age ( Results Overall, 1048 patients were randomized. At week 48, numerically greater proportions of patients achieved PASI 90, PASI 100, IGA 0/1, and IGA 0 with guselkumab vs. secukinumab regardless of baseline age, body weight, BMI, disease severity, body region, and prior medication. The largest differences were in patients ≥65 years old and patients weighing >100 kg. Conclusions Guselkumab treatment provided greater efficacy vs. secukinumab at week 48 in most subpopulations of patients with psoriasis.

The resources in the Internet of Things (IoT) network are distributed among different parts of the network. Considering huge number of IoT resources, the task of discovering them is challenging. While registering them in a centralized server such as a cloud data center is one possible solution, but due to billions of IoT resources and their limited computation power, the centralized approach leads to some efficiency and security issues. In this paper we proposed a location aware and decentralized multi layer model of resource discovery (LaMRD) in IoT. It allows a resource to be registered publicly or privately, and to be discovered in a decentralized scheme in the IoT network. LaMRD is based on structured peer-to-peer (p2p) scheme and follows the general system trend of fog computing. Our proposed model utilizes Distributed Hash Table (DHT) technology to create a p2p scheme of communication among fog nodes. The resources are registered in LaMRD based on their locations which results in a low added overhead in the registration and discovery processes. LaMRD generates a single overlay and it can be generated without specific organizing entity or location based devices. LaMRD guarantees some important security properties and it showed a lower latency comparing to the cloud based and decentralized resource discovery.

Objective Obesity is associated with severe COVID‐19 infection. Disease severity is associated with a higher COVID‐19 antibody titer. We compared the COVID‐19 antibody titer response of patients with obesity versus patients without obesity. Methods We retrospectively retrieved data of individuals tested for COVID‐19 serology at the Mount Sinai Health System in New York City between March 1st, 2020, and December 14th, 2021. The primary outcome was peak antibody titer, assessed as a binary variable (1:2880, which was the highest detected titer, versus lower than 1:2880). In patients with positive serology test, peak titer rates were compared between BMI groups (

This article presents the integration of a 32-channel neuromodulation system on chip (SoC) that is developed for chronic implantation in humans. The application-specific integrated circuit (ASIC) offers low-noise recording, a state-of-the-art (SotA) neurostimulator capable of both current- and voltage-controlled stimulation with high-voltage compliance, on-chip 16-bit data digitization as well as safety features such as electrode impedance estimation and charge balancing. The chip communicates through two distinct SPI interfaces for independent command and data transfer. Thus, the developed system constitutes a fully digital, bidirectional 32-channel interface to the brain.

Oral human papillomavirus (HPV) is associated with increasing rates of HPV-associated oropharyngeal cancer (OPC) in men. Sequential infection from one site to another has been demonstrated at the cervix and anus. Thus, risk of an oral HPV infection following a genital infection of the same type in the HPV Infection in Men study was investigated. Samples from 3,140 men enrolled in a longitudinal cohort were assessed for sequential genital to oral infection with one of nine HPV types (HPV 6, 11, 16, 18, 31, 33, 45, 52, 58); and then also sequential, same-type oral to genital infection. Incidence rate ratios (IRRs) compared rates of oral HPV among men with and without prior genital infection of the same type. Risk of sequential HPV infections were assessed using Cox proportional hazards model. Incidence of an oral HPV infection was significantly higher among men with a prior genital infection of the same type for any of the 9 HPV types (IRR: 2.3; 95% CI: 1.7–3.0). Hazard ratio of a sequential genital to oral HPV infection was 2.3 (95% CI: 1.7–3.1) and 3.5 (95% CI: 1.9–6.4) for oral to genital infection. Both changed minimally after adjustment for age, country, circumcision, alcohol use, lifetime sexual partners and recent oral sex partners. HPV infections at one site could elevate risk of a subsequent genital or oral HPV infection of the same type in men, emphasizing the importance of vaccination to prevent all HPV infections.

BACKGROUND Secukinumab [an interleukin (IL)-17A inhibitor] has demonstrated significantly higher efficacy vs. etanercept (a tumour necrosis factor inhibitor) and ustekinumab (an IL-12/23 inhibitor) in patients with moderate-to-severe plaque psoriasis. OBJECTIVES To report 52-week results from a prespecified analysis of patients with active psoriatic arthritis (PsA) having concomitant moderate-to-severe plaque psoriasis from the head-to-head EXCEED monotherapy study comparing secukinumab with adalimumab. METHODS Patients were randomized to receive secukinumab 300 mg via subcutaneous injection at baseline, week 1-4, and then every 4 weeks until week 48 or adalimumab 40 mg via subcutaneous injection every 2 weeks from baseline until week 50. Assessments in patients with concomitant moderate-to-severe psoriasis, defined as having affected body surface area > 10% or Psoriasis Area and Severity Index (PASI) ≥ 10 at baseline, included musculoskeletal, skin and quality-of-life outcomes. Missing data were handled using multiple imputation. RESULTS Of the 853 patients [secukinumab (N = 426), adalimumab (N = 427)], 211 (24·7%) had concomitant moderate-to-severe psoriasis [secukinumab (N = 110, 25·8%), adalimumab (N = 101, 23·7%)]. Up to week 50, 5·5% of patients discontinued secukinumab vs.17·8% in the adalimumab group. The proportion of patients who achieved American College of Rheumatology (ACR) 20 response was 76·4% with secukinumab vs. 68·3% with adalimumab (P = 0·175), PASI 100 response was 39·1% vs. 23·8% (P = 0·013), and simultaneous improvement in ACR 50 and PASI 100 response at week 52 was 28·2% vs. 17·7%, respectively (P = 0·06). Secukinumab demonstrated consistently higher responses vs. adalimumab across skin endpoints. CONCLUSIONS This prespecified analysis in PsA patients with concomitant moderate-to-severe plaque psoriasis in the EXCEED study provides further evidence that IL-17 inhibitors offer a comprehensive biological treatment to manage the concomitant features of psoriasis and PsA.

ZusammenfassungDurch die Einführung der sog. Krebsfährtensuche mittels Kolposkopie, Zytologie und Histopathologie durch Ernst Navratil (1902–1977) im Jahr 1946 kam es zu einem markanten Aufschwung der Gynäkopathologie an der Grazer Univ.-Frauenklinik. Dieser Aufschwung war im Wesentlichen Fritz Bajardi (1918–2006) und Erich Burghardt (1921–2006) zu verdanken. Diese haben in der Zeit ihrer klinischen Tätigkeit durch ihre Zusammenarbeit wesentliche Erkenntnisse über die Pathogenese des Zervixkarzinoms geliefert. Erich Burghardt ist es im Besonderen zu verdanken, dass die in der Literatur verstreuten diesbezüglichen Publikationen in einem synoptischen Werk zusammengefasst wurden. Es werden die richtungsweisenden Forschungsergebnisse von Bajardi und vor allem von Burghardt im Lichte des heutigen Erkenntnisstandes diskutiert.